Monocyte-chemoattractant protein-1 Levels in Human Atherosclerosis Associate with Plaque Vulnerability

Marios K. Georgakis,^{1, a} Sander W. van der Laan,^{2, a} Yaw Asare,¹ Joost M. Mekke,³ Saskia Haitjema,⁴ Arjan H. Schoneveld,⁴ Dominique P.V. de Kleijn,³ Gert J. de Borst,³ Gerard Pasterkamp,⁴ Martin Dichgans^{1, 5, *}

¹ Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany ² Laboratory of Experimental Cardiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands ³ Department of Vascular Surgery, Division of Surgical Specialties, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands ⁴ Center Diagnostic Laboratory, Division Laboratories and Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands ⁵ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany

^a contributed equally

Abstract

Monocyte chemoattractant protein-1 (MCP-1) recruits monocytes to the atherosclerotic plaque. While experimental,1-6 genetic,7 and observational8,9 data support a key role of MCP-1 in atherosclerosis, the translational potential of targeting MCP-1 signaling for lowering vascular risk is limited by the lack of data on plaque MCP-1 activity in human atherosclerosis. Here, we measured MCP-1 levels in human plaque samples from 1,199 patients undergoing carotid endarterectomy and explored associations with histopathological, molecular, and clinical features of plaque vulnerability. MCP-1 plaque levels were associated with histopathological hallmarks of plaque vulnerability (large lipid core, low collagen, high macrophage burden, low smooth muscle cell burden, intraplaque hemorrhage) as well as molecular markers of plaque inflammation and matrix turnover, clinical plaque instability, and periprocedural stroke during plaque removal. Collectively, our findings highlight a role of MCP-1 in human plaque vulnerability and suggest that interfering with MCP-1 signaling in patients with established atherosclerosis could lower vascular risk.

Figure 1. Design of this study.

Analysis Scripts

Surely these scripts will not work immediately on your systems, but they may be used and edited for local use.

• 2020_georgakis_vanderlaan_MCP1.Rmd
  R Notebook in R markdown with all.
• 2020_georgakis_vanderlaan_MCP1.nb.html
  R Notebook in HTML to explore summary statistics between models 1, 2, and 3. Also creates files for plotting.

Data availability

The data is available upon request through a MTA/DTA due to consent restrictions and EU/NL laws and regulations.

Notes

Scripts will work within the context of a certain Linux environment, for example a CentOS7 system on a SUN Grid Engine background or macOS X Lion+ (version 10.7.[x]+).

Versions

• v1.0.0 Initial version.

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